Introduction
Fatigue, defined as “an overwhelming sense of tiredness, lack of energy and feeling of exhaustion” [1] is a frequent complaint in celiac disease. A strict, lifelong gluten free diet is the only established treatment for celiac disease, however its long-term effect on fatigue is unknown.
Aims & Methods
Our aims were to investigate the course of fatigue severity and prevalence in celiac patients from diagnosis to five to seven years on a gluten free diet, and to investigate whether diet adherence, disease activity and selected biochemical markers are associated with fatigue.
We conducted a single-center prospective study in 45 patients with newly diagnosed celiac disease. The primary endpoints were fatigue severity, as measured by the Fatigue Severity Scale (FSS) [2], the fatigue Visual Analog Scale (fVAS) [3], and the Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs) [4]. SF-36vs scores were inverted (100 – SF-36vs = inverted SF-36vs) to ease comparison between the other scales, so that higher scores indicate more fatigue. Clinically relevant fatigue was defined by an FSS score of ≥4, a fVAS score of ≥50, and an inverted SF-36vs score of ≥65. Study visits were performed at the time of diagnosis (Visit 1), after adhering to a gluten free diet for one year (Visit 2) and for five to seven years (Visit 3). Diet adherence was evaluated through urinary gluten immunogenic peptides (GIP) and the Celiac Diet Adherence test (CDAT) [5]. Disease activity was assessed through Celiac Symptom Index (CSI) [6], celiac autoantibodies (anti tissue transglutaminase IgA and deamidated gliadin peptide IgG) and histologic evaluation (Marsh score). Nutritional status was assessed through BMI, hemoglobin, 25-hydroxy vitamin D, cobalamin, ferritin and folic acid levels.
Results
Fatigue severity was significantly reduced from time of diagnosis, for all three instruments (Table 1). Fatigue prevalence rates were significantly decreased from Visit 1 (40-53%) to Visit 3 (27-31%). Fatigue was significantly lower in patients with good adherence compared to patients with poor adherence according to CDAT scores (For FSS p=0.022, fVAS p=0.017, and for inverted SF-36vs p=0.033). There was however no difference in fatigue severity between adherent and nonadherent patients when evaluating adherence through urinary GIP. Fatigue was lower in patients in clinical remission according to CSI scores (for FSS p=0.002, fVAS p=0.004, and for inverted SF-36vs p=0.002), but not associated with autoantibodies or nutritional status. In multiple linear regression analysis, depression was the only independent variable significantly associated with all three fatigue measures at Visit 3, whereas pain was positively associated with inverted SF-36vs scores.
Table 1.
Fatigue instrument
| Visit 1
| Visit 2
| Visit 3
| Change from Visit 1 to Visit 3 (95% CI)
| P-value Visit 1 vs. Visit 3
| P-values across three time points (Visit 1, 2 and 3)
|
FSS
| 3.7 (2.2-5.0)
| 1.9 (1.5 - 3.3)
| 2.3 (1.3 - 4.2)
| -0.5 (-1.2 – -0.2
| 0.012
| <0.001
|
fVAS
| 45 (16.5-68.5) | 15 (9.0 - 41.0)
| 21 (4.0 - 56.0)
| -10 (-23.0 – -3.0)
| 0.003
| 0.001
|
SF-36vs (inverted)
| 65.0 (40.0-77.5)
| 30.0 (25.0 - 47.5)
| 45.0 (30.0 - 70.0)
| -5.0 (-10 – 0)
| 0.006
| <0.001
|
Conclusion
Fatigue remains a frequent complaint in celiac disease even after five to seven years on a gluten free diet. However, fatigue severity is reduced from time of diagnosis. Fatigue was associated with dietary adherence as assessed by CDAT. Disease activity according to CSI was associated with fatigue, whereas nutritional status, autoantibodies and histologic changes were not.
References
1. Krupp, L.B. and D.A. Pollina, Mechanisms and management of fatigue in progressive neurological disorders. Curr Opin Neurol, 1996. 9(6): p. 456-60.
2. Krupp, L.B., et al., The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol, 1989. 46(10): p. 1121-3.
3. Wolfe, F., Michaud K, Pincus T, Preliminary evaluation of a visual analog function scale for use in rheumatoid arthritis. J Rheumatol, 2005. 32(7): p. 1261-6.
4. Ware, J.E., Jr. and C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 1992. 30(6): p. 473-83.
5. Leffler, D.A., et al., A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(5): p. 530-6, 536.e1-2.
6. Leffler, D.A., et al., A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(12): p. 1328-34, 1334.e1-3.
Disclosure
Berit Mære Skjellerudsveen: Received lecture honoraria from Takeda for lectures on IBD and pregnancy. This study is partly funded by a grant from the patient organization “The Norwegian Coeliac Society”.